[Vascular targeted photodynamic therapy in low-risk prostate cancer. A literature review]. / Photothérapie dynamique dans le cancer de la prostate à faible risque. Revue de la littérature.

INTRODUCTION: Currently, about 50% of newly prostate cancers are localized and low-risk according to D'Amico risk classification. Focal therapies whose objective is to treat only the index lesion appear as a new alternative being evaluated in the management of these cancers. Besides the interest in the control of the disease, focal therapies present a very low risk of morbidity. Vascular targeted photodynamic therapy (VTP) is one of these new emerging therapies. METHOD: An exhaustive review concerning VTP in prostate cancer was carried out. A search by the following keywords "low-risk prostate cancer", "focal treatment", "vascular targeted photodynamic therapy" "TOOKAD" was carried out in Pubmed and Embase. RESULTS: In phase II studies, VTP showed a rate of 80% negative biopsies at 6 months, with good clinical tolerance. The European phase III, randomized prospective study, comparing VTP to active surveillance showed a lower proportion of progression, as well as a more significant duration before progression for VTP. The adverse events are mostly moderate and transient. The quality of life of patients is preserved, with a moderate impact on erectile and urinary functions. CONCLUSION: VTP appear to be a promising new approach in localized low-risk prostate cancer.

Who is dying after nephrectomy for cancer? Study of risk factors and causes of death after analyzing morbidity and mortality reviews (UroCCR-33 study).

BACKGROUND AND METHODS: Nephrectomy is the treatment for renal cell cancer from T1-4 tumors but remains at risk. To determine the thirty-day mortality rate after nephrectomy for cancer and to identify causes and risk factors of death in order to find clinical applications. From 2014 to 2017, we performed a retrospective multicentric analysis of prospectively collected data study involving the French network for research on kidney cancer (UroCCR). All patients who died after nephrectomy for cancer during the first thirty days were identified. Patients' characteristics, causes of death and morbidity and mortality reviews reports were analyzed for each death. RESULTS AND LIMITATIONS: In total, 2578 patients underwent nephrectomy and 35 deaths occurred. The thirty-day mortality rate was 1.4%. In univariate analysis, symptoms at diagnosis (P=0.006, OR=2.56 IC (1.3-5.03)), c stage superior to cT1 (P<0.0001, OR=6.13 IC (2.8-13.2)), cT stage superior to cT2 (P<0.0001, OR=8.8 IC (4.39-17.8)), nodal invasion (P<0.0001, OR=4.6 IC (1.9-10.7)), distant metastasis (P=0.001, OR=4.01 IC (1.7-8.9)), open surgery (P<0.0001, OR=0.272 IC (0.13-0.54)) and radical nephrectomy (P=0.007, OR=2.737 IC (1.3-5.7)) were risk factors of thirty-day mortality. In a multivariable model, only cT stage superior to T2 (P=0.015, OR=3.55 IC (1.27-10.01)) was a risk factor of thirty-day mortality. The main cause of postoperative death was pulmonary (n=15; 43%). The second cause was postoperative digestive sepsis for 7 patients (20%). Only 2 morbidity and mortality reviews had been done for the 35 deaths. Limitations are related to the thirty-day mortality criteria and descriptive study design. CONCLUSIONS: Symptomatic patients, stage cTNM and type and techniques of surgery are determinants of thirty-day mortality after nephrectomy for cancer. The first cause of postoperative death is pulmonary. Morbidity and mortality reviews should be considered to better understand causes of death and to reduce early mortality after nephrectomy for cancer. LEVEL OF EVIDENCE: 4.

Urinary morbidity after 125I brachytherapy of the prostate.

OBJECTIVE: To assess urinary morbidity within the first 6 months after transperineal prostate brachytherapy (TPBT) with 125I for localized prostate adenocarcinoma. PATIENTS AND METHODS: Between September 2000 and July 2001, 50 consecutive patients with favourable early-stage prostate cancer were treated with TPBT. Clinical and objective investigations, including uroflowmetry and postvoid residual urine measurements, were evaluated for short-term urinary morbidity; predictive factors were also sought. RESULTS: Thirty-eight (76%) patients developed urinary disorders, but severe urinary complications were exceptional. The International Prostate Symptom Score (IPSS) changed significantly during the first and third month after implantation and then improved during the sixth month. Concomitantly, the maximum and the average urinary flow rate deteriorated significantly. The variations in postvoid residual were less significant. An initial IPSS of > 8 and previous alpha-blocker treatment were identified as significant predictive factors of urinary morbidity, as were the TPBT dose received by 90% of the target volume and by 30% of the urethra, and the volume of prostate receiving 144 Gy. CONCLUSION: Urinary morbidity after TPBT is frequent but rarely exceptionally severe; patients must therefore be given full information. Patients with a higher initial IPSS or having had previous alpha-blocker treatment, with their associated dosimetric factors, are at greater risk of these urinary morbidity.

Segregation analysis of prostate cancer in France: evidence for autosomal dominant inheritance and residual brother-brother dependence.

Four segregation analyses concerning prostate cancer (CaP), three conducted in the United States and one in Northern Europe, have shown evidence for a dominant major gene but with different parameter estimates. A recent segregation analysis of Australian pedigrees has found a better fit of a two-locus model than single-locus models. This model included a dominantly inherited increased risk that was greater at younger ages and a recessively inherited or X-linked increased risk that was greater at older ages. Recent linkage analyses have led to the detection of at least 8 CaP predisposing genes, suggesting a complex inheritance and genetic heterogeneity. To assess the nature of familial aggregation of prostate cancer in France, segregation analysis was conducted in 691 families ascertained through 691 CaP patients, recruited from three French hospitals and unselected with respect to age at diagnosis, clinical stage or family history. This mode of family inclusion, without any particular selection of the probands, is unique, as probands from all previous analyses were selected according to various criteria. Segregation analysis was carried out using the logistic hazard regressive model, as incorporated in the REGRESS program, which can accommodate a major gene effect, residual familial dependences of any origin (genetic and/or environmental), and covariates, while including survival analysis concepts. Segregation analysis showed evidence for the segregation of an autosomal dominant gene (allele frequency of 0.03%) with an additional brother-brother dependence. The estimated cumulative risks of prostate cancer by age 85 years, among subjects with the at-risk genotype, were 86% in the fathers' generation and 99% in the probands' generation. This study supports the model of Mendelian transmission of a rare autosomal dominant gene with high penetrance, and demonstrates that additional genetic and/or common sibling environmental factors are involved to account for the familial clustering of CaP.

[Acute urinary complications after prostate iodine-125 brachytherapy: evaluation and risk factors]. / Les complications urinaries aiguës de la curiethérapie prostatique par iode-125: évaluation et facteurs de risque.

PURPOSE: Evaluation of acute urinary toxicity following prostate Iodine-125 brachytherapy and determination of risk factors. PATIENTS AND METHODS: Between September 2000 and July 2001, 50 men were entered into the study. A clinical follow-up accompanied by an objective measurement of urinary morbidity, including uroflowmetry and post-void residue, enabled the evaluation of acute toxicity before and then at one, three and six months of the implantation. Predictors were also searched for. RESULTS: 38 (76%) patients developed urinary disorders but those remained minor or moderate. The IPSS, as well as uroflowmetry deteriorated significantly at the first and third month post-implant, before improving during the sixth month. Besides, the variations of the post-void residue were less significant. Concerning the factors of risk, an initial IPSS superior to eight and a prior alpha-blocker treatment were the preoperative identified risk factors. Regarding dosimetric parameters, preoperative U30 and postoperative D90, D95, V100, V150 and V200 were identified. CONCLUSION: Though remaining minor or moderate, the great frequency of acute urinary toxicity following prostate brachytherapy requires frank and open dialogue with the patient in conjunction with an evaluation of the urinary status before implantation Patients with higher initial IPSS or having required a prior alpha-blocker treatment are more exposed to these disorders and their correlated postoperative dosimetric factors.

Prostate carcinoma risk and allelic variants of genes involved in androgen biosynthesis and metabolism pathways.

BACKGROUND: Ethnicity, when it is used to mean shared genetic inheritance within a group, has become one of the most important factors in determining prostate carcinoma risk. Genetic polymorphisms were hypothesized to be the probable explanation for differences in risk among ethnic groups. The authors evaluated the association between polymorphisms in genes involved in the androgen biosynthesis and metabolism pathway and the risk of prostate carcinoma. METHODS: Two hundred twenty-six patients with the pathologic diagnosis of sporadic prostate tumor and 156 healthy matched (age, ethnic group) male controls from a large epidemiologic cohort were genotyped for previously described polymorphisms in the androgen receptor (AR), 5alpha-reductase type II (SRD5A2), p450c17 (CYP17), and aromatase (CYP19) genes. The different polymorphisms in prostate carcinoma patients also were analyzed according to age of onset, preoperative prostate-specific antigen level, tumor stage, and tumor grade. RESULTS: The distribution of the tetranucleotide simple tandem repeat polymorphism (STRP) in intron 4 of CYP19 was significantly different in control and cancer patients (P = 0.012). The 171 allele and the 187 allele were associated with prostate carcinoma risk (P = 0.05 and P = 0.045, respectively). Conversely, no association was observed between prostate carcinoma risk and the other polymorphisms studied as follow: the CAG repeat in exon 1 of AR, the (TA)n dinucleotide repeat polymorphism in the 3' untranslated region, and the A49T or V89L substitutions in SDR5A2, the single base pair (bp) (a T to C transition) polymorphism that creates an additional Sp1-type (CCACC box) promoter site in CYP17. In prostate carcinoma patients, CAG repeats of AR, and TA repeats of SDR5A2 are associated with age of onset (P = 0.05 and P < 0.001, respectively). CONCLUSIONS: The association between the 171-bp allele of CYP19 and prostate carcinoma risk suggests that aromatase could be used as a new indicator for prostate carcinoma prevention in men of White French ethnogeographic origin. Conversely, it is possible that an individual carries both a high- and a low-risk marker (e.g., CYP17 A2 allele and V89L in SRD5A2) resulting in no overall difference in risk observed across the population. For these reasons, the development of a polygenic model, incorporating multiple loci from the individual genes may maximize the chance of identifying individuals with high-risk genotypes.

Early-onset hereditary prostate cancer is not associated with specific clinical and biological features.

BACKGROUND: Familial prostate cancer (CaP) accounts for 15-20% of all CaP, and hereditary CaP for 5-10% of patients. Few data are available concerning their clinical and biological features. METHODS: We compared diagnostic modalities, age, clinical stage, PSA, and tumor grade at diagnosis in CaP patients according to familial CaP profile: hereditary (HR) (> or =3 CaP), familial nonhereditary (FNH) (= 2 CaP), and sporadic CaP. Only cases diagnosed after January 1, 1987 (PSA-available period) were included. We considered as informative sporadic (IS) cases those probands with 2+ nonaffected brothers at least 50 years old. Finally, 267 CaP (230 probands and 37 affected brothers) were studied. RESULTS: In multivariate analysis, the only specific parameter significantly associated with HR and FNH CaP was early age at diagnosis; mean ages were 65.3 years (HR), 67 years (FNH), and 70.9 years (IS) (P < 0. 0001). No significant difference was observed concerning clinical stage, PSA, and tumor grade. In addition, diagnostic modalities were similar in the three groups. CONCLUSIONS: Our data confirm the occurrence of early-onset CaP in hereditary families. Although the clinical and biological presentation of HR CaP remains controversial, the lack of specific features observed in our study leads us to conclude that there is no difference in the aggressiveness of the disease in hereditary compared to sporadic CaP.

[Epidemiology of familial prostatic cancer: 4-year assessment of French studies]. / Epidémiologie du cancer de la prostate familial: bilan à 4 ans des études françaises.

OBJECTIVES: (1) To determine the frequency of familial (at least 2 cases) and hereditary forms of prostate cancer (CaP), (2) to define the results according to the patient's age at diagnosis, as various epidemiological studies have demonstrated a possible familial aggregation of CaP in about 15 to 25% of cases. Carter's familial segregation study (P.N.A.S. 1992, 89, 3367-71) showed that a genetic predisposition, with autosomal dominant transmission, could be responsible for 9% of all cases of prostate cancer. MATERIAL AND METHODS: We conducted a systematic genealogy study of patients suffering from newly diagnosed CaP or followed for known CaP in 3 French urological centres, by means of questionnaires completed by the patients. Subsequently, a national collection of families with at least 2 cases of CaP identified families with hereditary forms of CaP. Hereditary cases were considered to be those presenting at least: one CaP in three 1st degree relatives, or 3 cases over 3 generations in the same branch of the family (paternal or maternal), or finally 2 early cases before the age of 55 years. Statistical analysis used the univariate logistic regression test between family status and the medical centre or the patient's age at diagnosis. RESULTS: From July 1994 onwards, we included 801 patients (all stages combined) in the systematic study and 110 patients (13.7%) were excluded (refusal to participate, advanced age). For 691 of the families studied (Brest: 225, Nancy: 249, Paris St Louis: 217), we observed 32 (14.2%), 29 (11.6%), 37 (17.1%) of familial forms (mean: 14.2%) and 11 (4.9%), 6 (2.4%), 8 (3.7%) of hereditary forms (mean: 3.6%), respectively (no significant differences between centres). Analysis of the results according to age at diagnosis of CaP also showed a higher incidence of familial (significant difference) and hereditary forms (limit of significance) for CaP occurring at a younger age (before 65 years). The national collection collected a total of 624 familial forms of CaP, including 236 (37.8%) cases of hereditary forms; 115 families were informative for the genetic linkage study. CONCLUSION: These results confirm the data of earlier studies, revealing about 15 to 25% of familial forms of CaP and 5 to 10% of hereditary forms. Similarly, the systematic study confirmed the earlier onset of CaP in patients with a genetic predisposition. These data therefore encourage systematic questioning of patients for a family history of CaP in order to propose targeted screening of high-risk subjects in the families concerned and to intensify identification of hereditary forms in order to investigate the genes involved.